The combination of inhaled corticosteroids and
long-acting β2-adrenoceptor agonists is increasingly used
in chronic obstructive pulmonary disease (COPD). Recently,
we have demonstrated that combination of salmeterol
and fluticasone propionate (FP) additionally suppress the
production of IL-8 by human monocyte. In this study, the
molecular mechanism behind the effectiveness of this
combination therapy is investigated in human neutrophils.
Human ... read more neutrophils were preincubated with salmeterol or
FP or the combination. The amount of interleukin-8 (IL-8),
elastase and matrix metalloproteinases (MMP)-2 and -9
releases, and reactive oxygen species (ROS) generation and
expression of MAP kinase phosphatase (MKP-1) and
glucocorticoid receptor (GR) were determined. Cigarette
smoke medium (CSM) induces an increased expression of
CXC receptors and the production of ROS that may explain
the strong production of IL-8 by neutrophils. The expression
of CXC receptors, the production of ROS, and the
release of elastase and MMP-2 and -9 were not influenced by salmeterol, FP, or the combination. Interestingly, the
combination therapy had an additive suppressive effect on
the CSM-induced production of IL-8. The latter could be
explained by an increased mRNA expression of MKP-1,
the GR and an increased translocation of the GR to the
nucleus. This leads eventually to suppression of both the NF-κB and MAPK pathways and, hence, to less IL-
8 production by the neutrophil. These data are in support
for the use of a combination therapy in COPD patients. show less